Clinical Trial of Sarilumab in Adults With COVID-19 (SARICOR)

Clinical Trial of Sarilumab in Adults Hospitalized With COVID-19 Presenting Cytokine Release Syndrome

Early administration of sarilumab in hospitalized patients infected with COVID-19 who have pulmonary infiltrates and are at high risk of unfavorable evolution could decrease/prevent progression to acute respiratory distress syndrome (ARDS) requiring high flow nasal oxygenation (HFNO) or either invasive or non-invasive mechanical ventilation.

Study Overview

• Status: Completed
• Conditions: SARS-CoV 2; SARS
• Intervention / Treatment: Drug: Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA]; Drug: Sarilumab 400 MG/2.28 ML Subcutaneous Solution [KEVZARA]; Drug: Best available treatment

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years and <75 years
• Admission for confirmed respiratory symptoms to COVID-19 based on a positive PCR in a sample of the respiratory tract in the local laboratory in the absence of respiratory distress syndrome requiring ONAF or mechanical ventilation
• Interstitial pneumonia confirmed by chest radiography or CT
• IL-6 levels> 40 pg / ml. In its absence, D-Dimer (DD)> 1500 or> 1000 may be included if progressive increases are documented
• Negative pregnancy test in women of childbearing age
• Signature of informed consent

Exclusion Criteria:

• SOFA score> 6 points
• Patient who, in the researcher's opinion, is not a subsidiary of invasive mechanical ventilation
• Neutrophil count <2 x 103 / μL
• Platelet count <100 x 103 / μL
• ALT or AST levels> 5 times the upper limit of normal
• Severe renal failure (CrCr <30 ml / min)
• Active bacterial infectious process
• Active tuberculosis, history of not completing treatment against tuberculosis, suspicion of extrapulmonary tuberculosis
• History of intestinal ulcer or diverticulitis
• History of hypersensitivity reactions to Sarilumab or its excipients
• Treatment with TNF antagonists
• Previous treatment with anti-IL6 in the previous 30 days
• Chronic prior treatment with corticosteroids at doses greater than 0.5 mg / kg / day of prednisone or equivalent. Yes, inhaled and topical corticosteroids are acceptable
• Concomitant treatment with immunomodulators, among which are Vitamin D or statins. Macrolides such as azithromycin are acceptable
• Patients on immunosuppressive treatment for any cause
• HIV-infected patients with CD4 <200 / mm3
• Past or current history of autoimmune disease or systemic inflammatory disease
• Patients who have received or are planning therapy with immunomodulatory antibodies, including immunoglobulins
• Participation in any clinical trial that evaluated any investigational product in the last 3 months or less than 5 half-lives of the investigational product
• Pregnancy
• Any other condition that, in clinical judgment, prevents adherence to the patient's protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sarilumab 200 mg; Subjects treated with the best available treatment up to 14 days plus Sarilumab 200 mg single dose.	Drug: Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA]; Best available treatment up to 14 days plus Sarilumab 200 mg
Experimental: Sarilumab 400 mg; Subjects treated with the best available treatment up to 14 days plus Sarilumab 400 mg single dose.	Drug: Sarilumab 400 MG/2.28 ML Subcutaneous Solution [KEVZARA]; Best available treatment up to 14 days plus Sarilumab 400 mg
Active Comparator: Control; Subjects treated with the best available treatment up to 14 days.	Drug: Best available treatment; Best available treatment up to 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilation requirements	Proportion of patients requiring or time (in days) until required: High flow nasal oxygenation (HFNO); Non-invasive mechanical ventilation type BiPAP; Non-invasive mechanical ventilation type CPAP; Invasive mechanical ventilation	At day 28 or when the subject is discharged (whichever occurs first)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Crude mortality	Crude mortality at 28 days	At day 28 or when the subject is discharged (whichever occurs first)
Time to clinical improvement	Time to clinical improvement: defined as the mean change or time in days from randomization to any of the following criteria: (i) improvement of two points on the ordinal scale of 7 points of severity or, (ii) hospital discharge with lifetime. The criteria reached before are used. The 7 point gravity scale includes the following categories: - Not hospitalized with normal activity; - Not hospitalized but unable to have normal activity; - Hospitalized, without requiring oxygen supplementation; - Hospitalized, requiring oxygen supplementation; - Hospitalized, requiring ONAF, non-invasive mechanical ventilation or both; - Hospitalized requiring ECMO, invasive mechanical ventilation or both; - Death	At day 28 or when the subject is discharged (whichever occurs first)
Time until improvement in oxygenation	Time (in days) until improvement in oxygenation for at least 48 hours: Time to verify an increase in the SpO2 / FiO2 ratio with respect to the worst SpO2 / FiO2 prior to treatment with Sarilumab and stratified according to levels of IL-6 or DD; Time to absence of oxygen requirement to maintain saturation in ambient air ≥ 93%; Number of days in need of supplemental oxygen	At day 28 or when the subject is discharged (whichever occurs first)
Proportion of patients requiring invasive mechanical ventilation	Proportion of patients requiring invasive mechanical ventilation in the trial	At day 28 or when the subject is discharged (whichever occurs first)
Proportion of patients having negative COVID-19 CRP at each visit	Proportion of patients having negative COVID-19 CRP at each visit of the trial	At day 28 or when the subject is discharged (whichever occurs first)
Mean of serum cytokine levels	Mean of serum cytokine levels: the panel of cytokines to quantify; IL1-��, IL1-β, IL6, IL8, IL10, IL12, IL18, IL38, INFɣ, TNF��, CCL2, CCL3, CCL4, MIF and PAI-1	At day 28 or when the subject is discharged (whichever occurs first)
Adverse events related to medication and its administration	Incidence of adverse events related to medication and its administration	At day 28 or when the subject is discharged (whichever occurs first)
Incidence in the appearance of serious bacterial, fungal or opportunistic infections	Incidence in the appearance of serious bacterial, fungal or opportunistic infections in the subjects	At day 28 or when the subject is discharged (whichever occurs first)
Incidence of perforation of the gastrointestinal tract	Incidence of perforation of the gastrointestinal tract in subjects	At day 28 or when the subject is discharged (whichever occurs first)
Leukocyte and neutrophil count	Leukocyte and neutrophil count mean	At day 28 or when the subject is discharged (whichever occurs first)
Hemoglobin levels	Mean hemoglobin levels	At day 28 or when the subject is discharged (whichever occurs first)
Platelet count	Platelet count mean	At day 28 or when the subject is discharged (whichever occurs first)
Levels of creatinemia	Average levels of creatinemia	At day 28 or when the subject is discharged (whichever occurs first)
Bilirubin levels	Average bilirubin levels	At day 28 or when the subject is discharged (whichever occurs first)
ALT and AST levels	ALT and AST average levels	At day 28 or when the subject is discharged (whichever occurs first)

Collaborators and Investigators

• Sponsor: Maimónides Biomedical Research Institute of Córdoba
• Collaborators: Consejería de Salud y Familias - Junta de Andalucía; Red Andaluza de Ensayos Clínicos en Enfermedades Infecciosas (Red ANCRAID)
• Investigators: Study Director: Julián de la Torre Cisneros, MD, Hospital Universitario Reina Sofia

Publications and helpful links

General Publications

• Merchante N, Carcel S, Garrido-Gracia JC, Trigo-Rodriguez M, Moreno MAE, Leon-Lopez R, Espindola-Gomez R, Alonso EA, Garcia DV, Romero-Palacios A, Perez-Camacho I, Gutierrez-Gutierrez B, Martinez-Marcos FJ, Fernandez-Roldan C, Perez-Crespo PMM, Cano AA, Leon E, Corzo JE, de la Fuente C, Torre-Cisneros J. Early Use of Sarilumab in Patients Hospitalized with COVID-19 Pneumonia and Features of Systemic Inflammation: the SARICOR Randomized Clinical Trial. Antimicrob Agents Chemother. 2022 Feb 15;66(2):e0210721. doi: 10.1128/AAC.02107-21. Epub 2021 Dec 13.
• Leon Lopez R, Fernandez SC, Limia Perez L, Romero Palacios A, Fernandez-Roldan MC, Aguilar Alonso E, Perez Camacho I, Rodriguez-Bano J, Merchante N, Olalla J, Esteban-Moreno MA, Santos M, Luque-Pineda A, Torre-Cisneros J. Efficacy and safety of early treatment with sarilumab in hospitalised adults with COVID-19 presenting cytokine release syndrome (SARICOR STUDY): protocol of a phase II, open-label, randomised, multicentre, controlled clinical trial. BMJ Open. 2020 Nov 14;10(11):e039951. doi: 10.1136/bmjopen-2020-039951.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2020
• Primary Completion (Actual): March 9, 2021
• Study Completion (Actual): April 6, 2021

Study Registration Dates

• First Submitted: April 20, 2020
• First Submitted That Met QC Criteria: April 20, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Actual): July 7, 2021
• Last Update Submitted That Met QC Criteria: July 6, 2021
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pharmaceutical Solutions
• Other Study ID Numbers: SARICOR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All the information will be published and it will be available in open access.
• IPD Sharing Time Frame: After the end of the trial.
• IPD Sharing Access Criteria: Contact uicec@imibic.org
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No